Minerals in the News Vol. 15, No. 12 (December 2017)

Hypoglycemic and Hypolipidemic Effects of Leucine, Zinc, and Chromium, Alone and in Combination, in Rats with Type 2 Diabetes

Biological Trace Element Research, December 2017, Volume 180, Issue 2, pp 246-254
Hassan S., et al.

(AA) For the increasing development of diabetes, dietary habits and using appropriate supplements can play important roles in the treatment or reduction of risk for this disease. The objective of this study was to investigate the effects of leucine (Leu), zinc (Zn), and chromium (Cr) supplementation, alone or in combination, in rats with type 2 diabetes (T2D). Seventy-seven adult male Wistar rats were randomly assigned in 11 groups, using nutritional supplements and insulin (INS) or glibenclamide (GLC). Supplementing Leu significantly reduced blood glucose, triglycerides (TG), nonesterified fatty acids (NEFA), low-density lipoprotein (LDL), and increased high-density lipoprotein (HDL) concentrations compared to vehicle-treated T2D animals, and those improvements were associated with reduced area under the 2-h blood glucose response curve (AUC). Supplementation of T2D animals with Zn improved serum lipid profile as well as blood glucose concentrations but was not comparable with the INS, GLC, and Leu groups. Supplementary Cr did not improve blood glucose and AUC in T2D rats, whereas it reduced serum TG and LDL and increased HDL concentrations. In conclusion, supplementation of diabetic rats with Leu was more effective in improving blood glucose and consequently decreasing glucose AUC than other nutritional supplements. Supplementary Zn and Cr only improved serum lipid profile. The combination of the nutritional supplements did not improve blood glucose level. Nevertheless, supplementation with Leu-Zn, Leu-Cr, Zn-Cr, and Leu-Zn-Cr led to an improved response in serum lipid profile over each supplement given alone. 
Serum and whole blood Zn, Cu and Mn profiles and their relation to redox status in lung cancer patients

Journal of Trace Elements in Medicine and Biology, Volume 45, January 2018, Pages 78-84
Katarzyna Z., et al.

(AA) Disturbed redox status may be critical to lung cancerogenesis, however little research has been conducted on general changes in total redox status in lung cancer. Levels and activities of antioxidants, especially enzymatic ones, are related to trace element concentration. Trace element status is often disturbed in cancers, however no studies concerning the association between redox and trace element status have been performed for lung cancer. We hypothesized that disturbed redox status in lung cancer patients is partially determined by trace elements while their distribution amongst blood compartments may differ compared to healthy subjects.

Blood samples from lung cancer patients (n = 44) and control subjects (n = 44) were collected to assess redox and trace element status. Serum and whole blood Cu and Mn levels were determined with GF-AAS, and Zn-with F-AAS. In serum the total antioxidant status (TAS) was determined with the commercial kit TAS (Randox, UK), total oxidant status (TOS) was determined based on the method developed by Erel and the oxidative stress index (OSI) was calculated. Total protein (T-Prot), albumin (Alb), uric acid (UA) and total bilirubin (T-Bil) concentrations were measured with an auto-analyser (Konelab 20i, Thermoscientific, USA), SOD and CAT activity − with commercially available kits (Cayman, USA).

The level of TAS, T-Prot, Alb, T-Bil, the activity of SOD, the concentration of whole blood Mn as well as serum and whole blood Zn were lower while TOS, OSI, serum Cu levels and serum Cu:Zn ratios were higher in lung cancer patients compared to the control group. In the lung cancer group TAS correlated positively with Alb and UA, serum Zn and negatively with whole blood Mn. Additionally, SOD positively correlated with the whole blood Mn and Cu:Zn ratio, while CAT − negatively with the whole blood Cu:Zn ratio. In the lung cancer sub-group at clinical stage I-II, TOS additionally negatively correlated with whole blood Zn, and CAT negatively with serum Cu and Cu:Zn ratio. In advanced lung cancer, we found a positive correlation between TAS and serum Zn, and a negative one − with serum Cu:Zn ratio. We observed a similar correlation between endogenous non-enzymatic antioxidants and TAS in the control group, however considerably fewer correlations between trace elements and antioxidants were observed.

This study supports the hypothesis that disturbed redox status in lung cancer patients is linked with alterations in trace element status regarding Zn, Mn and Cu. Moreover, the type of biological fluid influences both − alterations in the metal profile and relationships with redox status parameters.
Multi-micronutrient supplementation during pregnancy for prevention of maternal anemia and adverse birth outcomes in a high-altitude area: a prospective cohort study in rural Tibet of China

Br J Nutr. 2017 Sep;118(6):431-440. doi: 10.1017/S000711451700229X.
Kang Y., et al.

(AA) Anemia during pregnancy, characterised by Hb <110 g/l, is a specific risk factor for adverse maternal and perinatal outcomes in developing countries. The objective of this study was to determine the effectiveness of daily antenatal supplementation with multiple micronutrients (MMN) compared with folic acid (FA) on the occurrence of anemia among pregnant women and their infants' health in a high-altitude area. A prospective cohort study was carried out in two rural counties in Tibet from 2007 to 2012. A total of 1149 eligible pregnant women were allocated daily supplementation with FA in one county and MMN containing a recommended allowance of twenty-three vitamins and minerals in another county starting ≤24 weeks of gestation and continuing until delivery. Compared with the FA group, prenatal supplementation with MMN was significantly associated with reduced odds of anemia in the third trimester. This was demonstrated in the primary outcome, with an adjusted OR (AOR) of 0·63; 95 % CI 0·45, 0·88 and P=0·007 and also reduced odds of preterm delivery (AOR: 0·31; 95 % CI 0·15, 0·61; P=0·001). There was no difference between MMN and FA groups in mean birth weight (adjusted mean difference: 36·78; 95 % CI -19·42, 92·98 g; P=0·200), whereas MMN supplementation significantly reduced the odds of low-birth weight (LBW) babies (AOR: 0·58; 95 % CI 0·36, 0·91; P=0·019). In conclusion, the antenatal MMN supplementation in rural Tibet is associated with a reduction of maternal anemia in the third trimester, and may potentially decrease the risk of preterm delivery and LBW babies.
Multiple-micronutrient supplementation for women during pregnancy

Cochrane Database Syst Rev. 2017 Apr 13;4:CD004905. doi: 10.1002/14651858.CD004905.pub5.
Haider BA., et al.

Multiple-micronutrient (MMN) deficiencies often coexist among women of reproductive age in low- to middle-income countries. They are exacerbated in pregnancy due to the increased demands, leading to potentially adverse effects on the mother and developing fetus. Though supplementation with MMNs has been recommended earlier because of the evidence of impact on pregnancy outcomes, a consensus is yet to be reached regarding the replacement of iron and folic acid supplementation with MMNs. Since the last update of this Cochrane review, evidence from a few large trials has recently been made available, the inclusion of which is critical to inform policy.

To evaluate the benefits of oral multiple-micronutrient supplementation during pregnancy on maternal, fetal and infant health outcomes.

We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (11 March 2015) and reference lists of retrieved articles and key reviews. We also contacted experts in the field for additional and ongoing trials.

All prospective randomized controlled trials evaluating MMN supplementation with iron and folic acid during pregnancy and its effects on the pregnancy outcome were eligible, irrespective of language or the publication status of the trials. We included cluster-randomized trials, but quasi-randomized trials were excluded.


Nineteen trials (involving 138,538 women) were identified as eligible for inclusion in this review but only 17 trials (involving 137,791 women) contributed data to the review. Fifteen of these 17 trials were carried out in low and middle-income countries and compared MMN supplements with iron and folic acid versus iron with or without folic acid. Two trials carried out in the UK compared MMN with a placebo. MMN with iron and folic acid versus iron, with or without folic acid (15 trials): MMN resulted in a significant decrease in the number of newborn infants identified as low birthweight (LBW) (average risk ratio (RR) 0.88, 95% confidence interval (CI) 0.85 to 0.91; high-quality evidence) or small-for-gestational age (SGA) (average RR 0.92, 95% CI 0.86 to 0.98; moderate-quality evidence). No significant differences were shown for other maternal and pregnancy outcomes: preterm births (average RR 0.96, 95% CI 0.90 to 1.03; high-quality evidence), stillbirth (average RR 0.97, 95% CI 0.87, 1.09; high-quality evidence), maternal anemia in the third trimester (average RR 1.03, 95% CI 0.85 to 1.24), miscarriage (average RR 0.91, 95% CI 0.80 to 1.03), maternal mortality (average RR 0.97, 95% CI 0.63 to 1.48), perinatal mortality (average RR 1.01, 95% CI 0.91 to 1.13; high-quality evidence), neonatal mortality (average RR 1.06, 95% CI 0.92 to 1.22; high-quality evidence), or risk of delivery via a caesarean section (average RR 1.04; 95% CI 0.74 to 1.46).A number of prespecified, clinically important outcomes could not be assessed due to insufficient or non-available data. Single trials reported results for: very preterm birth < 34 weeks, macrosomia, side-effects of supplements, nutritional status of children, and congenital anomalies including neural tube defects and neurodevelopmental outcome: Bayley Scales of Infant Development (BSID) scores. None of these trials reported pre-eclampsia, placental abruption, premature rupture of membranes, cost of supplementation, and maternal well-being or satisfaction. When assessed according to GRADE criteria, the quality of evidence for the review's primary outcomes overall was good. Pooled results for primary outcomes were based on multiple trials with large sample sizes and precise estimates. The following outcomes were graded to be as of high quality: preterm birth, LBW, perinatal mortality, stillbirth and neonatal mortality. The outcome of SGA was graded to be of moderate quality, with evidence downgraded by one for funnel plot asymmetry and potential publication bias. We carried out sensitivity analysis excluding trials with high levels of sample attrition (> 20%); results were consistent with the main analysis except for the findings for SGA (average RR 0.91, 95% CI 0.84 to 1.00). We explored heterogeneity through subgroup analyses by maternal height and body mass index (BMI), timing of supplementation and dose of iron. Subgroup differences were observed for maternal BMI for the outcome preterm birth, with significant findings among women with low BMI. Subgroup differences were also observed for maternal BMI and maternal height for the outcome SGA, indicating a significant impact among women with higher maternal BMI and height. The overall analysis of perinatal mortality, although showed a non-significant effect of MMN supplements versus iron with or without folic acid, was found to have substantial statistical heterogeneity. Subgroup differences were observed for timing of supplementation for this outcome, indicating a significantly higher impact with late initiation of supplementation. The findings between subgroups for other primary outcomes were inconclusive. MMN versus placebo (two trials): A single trial in the UK found no clear differences between groups for preterm birth, SGA, LBW or maternal anemia in the third trimester. A second trial reported the number of women with pre-eclampsia; there was no evidence of a difference between groups. Other outcomes were not reported.


Our findings support the effect of MMN supplements with iron and folic acid in improving some birth outcomes. Overall, pregnant women who received MMN supplementation had fewer low birthweight babies and small-for-gestational-age babies. The findings, consistently observed in several systematic evaluations of evidence, provide a basis to guide the replacement of iron and folic acid with MMN supplements containing iron and folic acid for pregnant women in low and middle-income countries where MMN deficiencies are common among women of reproductive age. Efforts could focus on the integration of this intervention in maternal nutrition and antenatal care programs in low and middle-income countries.
A case of osteomalacia due to deranged mineral balance caused by saccharated ferric oxide and short-bowel syndrome: A case report.

Medicine (Baltimore). 2017 Sep;96(39):e8147. doi: 10.1097/MD.0000000000008147.
Nomoto H., et al.

Saccharated ferric oxide has been shown to lead to elevation of fibroblast growth factor 23, hypophosphatemia, and, consequently, osteomalacia. Moreover, mineral imbalance is often observed in patients with short-bowel syndrome to some degree.

A 62-year-old woman with short-bowel syndrome related with multiple resections of small intestines due to Crohn disease received regular intravenous administration of saccharated ferric oxide. Over the course of treatment, she was diagnosed with tetany, which was attributed to hypocalcemia. Additional assessments of the patient revealed not only hypocalcemia, but also hypophosphatemia, hypomagnesemia, osteomalacia, and a high concentration of fibroblast growth factor 23 (314 pg/mL).

We diagnosed her with mineral imbalance-induced osteomalacia due to saccharated ferric oxide and short-bowel syndrome.

Magnesium replacement therapy and discontinuation of saccharated ferric oxide alone.

These treatments were able to normalize her serum mineral levels and increase her bone mineral density.

This case suggests that adequate evaluation of serum minerals, including phosphate and magnesium, during saccharated ferric oxide administration may be necessary, especially in patients with short-bowel syndrome.